The proposed work involves the polyene macrolide antifungal antibiotics and includes the preparation by fermentation of a select variety of different commercially-unavailable polyene macrolides representative of the tetraenes, the pentaenes, the hexaenes, and the heptaenes; the isolation and purification of individual polyene macrolide components from complex fermentation products; the preparation of radioactive polyene macrolides by fermentation employing radiocarbon and tritium labelled biochemical precursors; the preparation of biologically-active polyene marcrolide derivatives including the water soluble salts of the methyl ester derivatives; the preparation of radioactive derivatives by chemical synthesis, carbon-14 and tritium double labelled amphotericin B methyl ester, candicidin methyl ester and amphotericin B sodium desoxycholate complex will be the major compounds to be prepared; the study in small laboratory animals of the metabolic fate and the pharmacological effects of various pure polyene macrolides and their derivatives by oral and parenteral routes of administration: the study of the nature of the acute and chronic toxicities of these compounds in small laboratory animals; the study of the in vitro and in vivo chemotherapeutic efficacy of these compounds based on the knowledge acquired from the above pharmacological and toxicological studies; and the availability of polyene macrolides and their synthetic derivatives, both unlabeled and carbon-14 and tritium labelled, for NIH authorized pharmacological, biochemical, and chemotherapeutic studies by other investigators. Amphotericin B methyl ester and amphotericin B sodium desoxycholate will be prepared for other investigators.